Abstract
To investigate the role of nitric oxide (NO), produced by the inducible form of NO synthase (NOS-2) in the development of experimental autoimmune uveoretinitis (EAU), we immunized C57BL/6x129Sv (H-2(b)) mice carrying a targeted disruption of the gene encoding NOS-2 (NOS-2[-/-]), and wild-type (WT) C57BL/6x129Sv controls with interphotoreceptor retinoid binding protein (IRBP). NOS-2[-/-] mice developed a clinical EAU with delayed onset and decreased severity compared to WT controls. The ocular tissues from WT mice contained activated F4/80 macrophages with NOS-2 expression and retinal destruction whereas less intense EAU was detected in NOS-2[-/-] mice. The expression of NOS-2 mRNA was detected in the retina at the peak of EAU in WT. Analysis of cytokine production in the spleen from NOS-2[-/-] mice by RT-PCR showed high levels of IL-10 mRNA. Our results demonstrate that NO is clearly involved in EAU and may be important for the regulation of immune responses through the regulation of IL-10.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoimmune Diseases / immunology
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Autoimmune Diseases / metabolism
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Cell Division
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Concanavalin A / pharmacology
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Eye Proteins*
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Female
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Gene Expression Regulation, Enzymologic / immunology
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Immunization
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Immunoglobulin G / blood
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Interferon-gamma / genetics
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Interferon-gamma / immunology
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Interleukin-10 / genetics
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Interleukin-10 / immunology
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Lymphocytes / cytology
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Lymphocytes / immunology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nitric Oxide / metabolism
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Nitric Oxide Synthase / genetics*
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Nitric Oxide Synthase Type II
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RNA, Messenger / analysis
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Retina / enzymology
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Retina / immunology
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Retinitis / immunology*
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Retinitis / metabolism*
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Retinol-Binding Proteins / immunology
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Retinol-Binding Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Severity of Illness Index
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Spleen / immunology
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
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Uveitis / immunology*
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Uveitis / metabolism*
Substances
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Eye Proteins
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Immunoglobulin G
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RNA, Messenger
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Retinol-Binding Proteins
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Tumor Necrosis Factor-alpha
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interstitial retinol-binding protein
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Concanavalin A
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Interleukin-10
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Nitric Oxide
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Interferon-gamma
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse